It has been demonstrated that the immunologic potential declines in old age. We have found that an increase in suppressor T cell activity is the first age-related immunologic lesion in mice. This is followed by a decrease in helper T cell function and finally by loss of B cell function. Spleens of mice treated with cyclophosphamide were found to contain cells capable of suppressing the secondary response of syngeneic and allogeneic spleen cells. These suppressor cells were not T cells, B cells, or macrophages. Conceivably, they may be involved in the establishment and maintenance of self-tolerance.